Intrinsic phase–amplitude coupling on multiple spatial scales during the loss and recovery of consciousness

Recent studies have demonstrated that changes in brain information processing during anesthetic-induced loss of consciousness (LOC) might be influenced by phase-amplitude coupling (PAC) in electroencephalogram (EEG). However, most anesthesia research on PAC typically focuses on delta and alpha oscillations. Studies of spatial-frequency characteristics by PAC for EEG may yield additional insights into understanding the impaired information processing under anesthesia unconsciousness and provide potential improvements in anesthesia monitoring.Considering different frequency bands of EEG represent neural activities on different spatial scales, we hypothesized that functional coupling simultaneously appears in multiple frequency bands and specific brain regions during anesthesia unconsciousness. In this paper, PAC analysis on whole-brain EEG besides delta and alpha oscillations was investigated to understand the influence of multiple cross-frequency coordination coupling on information processing during the loss and recovery of consciousness.EEG data from fifteen patients without cognitive diseases (7 males/8 females, aged 43.8 ± 13.4 years, weighing 63.3 ± 14.9 kilograms) undergoing lower limb surgery and sevoflurane anesthesia was recorded. To investigate the spatial-frequency characteristics of EEG source signals during loss and recovery of consciousness, the time-resolved PAC (tPAC) was calculated to reflect cross-frequency coordination in different frequency bands (delta, theta, alpha, beta, gamma) and different functional regions (Visual, Limbic, Dorsal attention, Ventral attention, Default, Somatomotor, Control, Salience networks). Furthermore, different patterns (peak-max and trough-max) of PAC were examined by constructing phase-amplitude histograms using phase bins to investigate the different information processing during LOC. The multivariate analysis of variance (MANOVA) and trend analysis were used for statistical analysis.Theta-alpha and alpha-beta PAC were observed during sevoflurane-induced LOC, which significantly changed during loss and recovery of consciousness (F4,70 = 16.553, p < 0.001 for theta-alpha PAC and F4,70 = 12.446, p < 0.001 for alpha-beta PAC, MANOVA test). Simultaneously, PAC was distributed in specific functional regions, i.e., Visual, Limbic, Default, Somatomotor, etc. Furthermore, peak-max patterns of theta-alpha PAC were observed while alpha-beta PAC showed trough-max patterns and vice versa.Theta-alpha and alpha-beta PAC observed in specific brain regions represent information processing on multiple spatial scales, and the opposite patterns of PAC indicate opposite information processing on multiple spatial scales during LOC. Our study demonstrates the regulation of local-global information processing during sevoflurane-induced LOC. It suggests the utility of evaluating the balance of functional integration and segregation in monitoring anesthetized states.